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Interleukin-34-dependent perivascular macrophages promote vascular function in the brain
Hannah Van Hove1, Chaim Glück2, Wiebke Mildenberger1
1Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.
Abstract:
The development of most macrophages depends on the colony-stimulating factor 1 (CSF-1) receptor, which has two ligands: CSF-1 and interleukin-34 (IL-34). While IL-34 is required for the homeostasis of microglia, the parenchymal macrophages in the central nervous system (CNS), it is unclear whether brain border-associated macrophages (BAMs) also depend on this cytokine. Here, we demonstrated that the embryonic development of murine BAMs in the choroid plexus, leptomeninges, and perivascular spaces required CSF-1, while IL-34 was critical for their maintenance in adulthood. In the brain, Il34 was expressed by mural cells and perivascular fibroblasts, and its transgenic deletion in these cells interrupted BAM maintenance. Il34 deficiency coincided with transcriptional changes in vascular cells, leading to increased flow velocity and vasomotion in pial and penetrating arterioles. Similarly, Mrc1CreCsf1rfl/fl mice lacking CD206+ perivascular BAMs exhibited increased hemodynamics in arterial networks. These findings reveal a crosstalk between vascular cells and CNS macrophages regulating cerebrovascular function.
Insights
Interleukin-34 (IL-34) is crucial for maintaining adult brain border-associated macrophages (BAMs), which are essential for regulating cerebrovascular function and CNS homeostasis.
Area of Science:
- Neuroimmunology
- Vascular Biology
- Macrophage Biology
Background:
- Colony-stimulating factor 1 (CSF-1) receptor signaling is vital for macrophage development.
- Interleukin-34 (IL-34) maintains microglia, but its role in brain border-associated macrophages (BAMs) is unknown.
Purpose of the Study:
- To investigate the role of IL-34 in the development and maintenance of BAMs.
- To explore the impact of BAM deficiency on cerebrovascular function.
Main Methods:
- Utilized murine models with genetic deletions of IL-34 in specific cell types.
- Employed lineage tracing and gene expression analysis.
- Assessed cerebrovascular hemodynamics in vivo.
Main Results:
- CSF-1 is required for embryonic BAM development, while IL-34 is critical for adult BAM maintenance.
- IL-34 deficiency in brain vascular cells leads to impaired BAM maintenance.
- Loss of BAMs results in altered vascular cell transcription and increased arterial flow velocity and vasomotion.
Conclusions:
- IL-34 plays a critical role in the adult maintenance of BAMs.
- A crosstalk exists between vascular cells and BAMs, regulating cerebrovascular function.
- These findings highlight a novel mechanism for CNS homeostasis maintenance.
